具有体外抗脂肪和抗胰岛素抵抗活性的响尾蛇毒肽组分的生物研究

IF 3.6 Q2 TOXICOLOGY Toxicon: X Pub Date : 2024-09-19 DOI:10.1016/j.toxcx.2024.100209
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引用次数: 0

摘要

动物毒液是天然产品,是新型分子的来源,为治疗多种疾病(包括 2 型糖尿病和肥胖症等代谢性疾病)的新型药物提供了灵感。从毒液中提取的毒素,如exendin-4(Heloderma suspectum)和crotamine(Crotalus durissus terrificus)已证明具有治疗肥胖症的潜力。此外,磷脂酶 A2 和崩解素等其他毒素也显示出在体外调节胰岛素分泌的潜力。这表明墨西哥响尾蛇毒液中具有潜在抗致肥性的毒肽种类还未被开发。因此,本研究通过抑制一氧化氮的产生,探讨了富含多肽的响尾蛇毒液对胰岛素抵抗、脂肪细胞脂质积累、抗氧化活性和炎症过程模型的体外效应。我们的研究结果表明,C. aquilus、C. ravus和C. scutulatus scutulatus的多肽富集部分能够恢复胰岛素抵抗,将葡萄糖消耗量提高到正常控制水平;C. culminatus、C. molossus oaxacus和C.c.s.salvini具有最显著的细胞抗氧化活性,对 ROS 的抑制率接近 80%。C.aquilus、C. pyrrhus 和 C. s. salvini 对一氧化氮产生的抑制率约为 85%。我们证明了这些来自克罗特鲁斯毒液的多肽在开发治疗 2 型糖尿病和肥胖症的新型药物方面的潜力。此外,我们首次在体外模型中描述了黄颡鱼毒多肽组分具有抗氧化和抗炎特性。
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Bioprospection of rattlesnake venom peptide fractions with anti-adipose and anti-insulin resistance activity in vitro
Animal venoms are natural products that have served as a source of novel molecules that have inspired novel drugs for several diseases, including for metabolic diseases such as type-2 diabetes and obesity. From venoms, toxins such as exendin-4 (Heloderma suspectum) and crotamine (Crotalus durissus terrificus) have demonstrated their potential as treatments for obesity. Moreover, other toxins such as Phospholipases A2 and Disintegrins have shown their potential to modulate insulin secretion in vitro. This suggests an unexplored diversity of venom peptides with a potential anti-obesogenic in Mexican rattlesnake venoms. For that reason, this study explored the in vitro effect of Crotalus venom peptide-rich fractions on models for insulin resistance, adipocyte lipid accumulation, antioxidant activity, and inflammation process through nitric oxide production inhibition. Our results demonstrated that the peptide-rich fractions of C. aquilus, C. ravus, and C. scutulatus scutulatus were capable of reverting insulin resistance, enhancing glucose consumption to normal control; C. culminatus, C. molossus oaxacus, and C. polystictus diminished the lipid accumulation on adipocytes by 20%; C. aquilus, C. ravus, and C. s. salvini had the most significant cellular antioxidant activity, having nearly 80% of ROS inhibition. C. aquilus, C. pyrrhus, and C. s. salvini inhibited nitric oxide production by about 85%. We demonstrated the potential of these peptides from Crotalus venoms to develop novel drugs to treat type-2 diabetes and obesity. Moreover, we described for the first time that Crotalus venom peptide fractions have antioxidant and inflammatory properties in vitro models.
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来源期刊
Toxicon: X
Toxicon: X Pharmacology, Toxicology and Pharmaceutics-Toxicology
CiteScore
6.50
自引率
0.00%
发文量
33
审稿时长
14 weeks
期刊最新文献
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